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Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes...

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Autores principales: Yu, Xinshuang, Dong, Peng, Yan, Yu, Liu, Fengjun, Wang, Hui, Lv, Yajuan, Song, Meijuan, Yao, Qingqiang, Hu, Sanyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490671/
https://www.ncbi.nlm.nih.gov/pubmed/34621754
http://dx.doi.org/10.3389/fcell.2021.748442
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author Yu, Xinshuang
Dong, Peng
Yan, Yu
Liu, Fengjun
Wang, Hui
Lv, Yajuan
Song, Meijuan
Yao, Qingqiang
Hu, Sanyuan
author_facet Yu, Xinshuang
Dong, Peng
Yan, Yu
Liu, Fengjun
Wang, Hui
Lv, Yajuan
Song, Meijuan
Yao, Qingqiang
Hu, Sanyuan
author_sort Yu, Xinshuang
collection PubMed
description Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P < 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P < 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8(+) T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P < 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.
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spelling pubmed-84906712021-10-06 Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer Yu, Xinshuang Dong, Peng Yan, Yu Liu, Fengjun Wang, Hui Lv, Yajuan Song, Meijuan Yao, Qingqiang Hu, Sanyuan Front Cell Dev Biol Cell and Developmental Biology Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P < 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P < 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8(+) T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P < 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer. Frontiers Media S.A. 2021-09-21 /pmc/articles/PMC8490671/ /pubmed/34621754 http://dx.doi.org/10.3389/fcell.2021.748442 Text en Copyright © 2021 Yu, Dong, Yan, Liu, Wang, Lv, Song, Yao and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Yu, Xinshuang
Dong, Peng
Yan, Yu
Liu, Fengjun
Wang, Hui
Lv, Yajuan
Song, Meijuan
Yao, Qingqiang
Hu, Sanyuan
Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title_full Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title_fullStr Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title_full_unstemmed Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title_short Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
title_sort identification of n6-methyladenosine-associated long non-coding rnas for immunotherapeutic response and prognosis in patients with pancreatic cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490671/
https://www.ncbi.nlm.nih.gov/pubmed/34621754
http://dx.doi.org/10.3389/fcell.2021.748442
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